More on VDR's Relationship to 1,25-D

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For those interested in the Vitamin D receptor and its relationship

to 1,25-D, here is another article;

FASEB J. 2005 Jul;19(9):1067-77.

Human cathelicidin antimicrobial peptide (CAMP) gene is a direct

target of the vitamin D receptor and is strongly up-regulated in

myeloid cells by 1,25-dihydroxyvitamin D3.

Gombart AF, Borregaard N, Koeffler HP.

Department of Medicine, Division of Hematology/Oncology, Cedars-Sinai

Medical Center, Geffen School of Medicine at UCLA, Los Angeles,

California 90048, USA. gombarta@...

The innate immune system of mammals provides a rapid response to

repel assaults from numerous infectious agents including bacteria,

viruses, fungi, and parasites. A major component of this system is a

diverse combination of cationic antimicrobial peptides that include

the alpha- and beta-defensins and cathelicidins. In this study, we

show that 1,25-dihydroxyvitamin D3 and three of its analogs induced

expression of the human cathelicidin antimicrobial peptide (CAMP)

gene. This induction was observed in acute myeloid leukemia (AML),

immortalized keratinocyte, and colon cancer cell lines, as well as

normal human bone marrow (BM) -derived macrophages and fresh BM cells

from two normal individuals and one AML patient. The induction

occurred via a consensus vitamin D response element (VDRE) in the

CAMP promoter that was bound by the vitamin D receptor (VDR).

Induction of CAMP in murine cells was not observed and expression of

CAMP mRNA in murine VDR-deficient bone marrow was similar to wild-

type levels. Comparison of mammalian genomes revealed evolutionary

conservation of the VDRE in a short interspersed nuclear element or

SINE in the CAMP promoter of primates that was absent in the mouse,

rat, and canine genomes. Our findings reveal a novel activity of 1,25-

dihydroxyvitamin D3 and the VDR in regulation of primate innate

immunity.

PMID: 15985530 [PubMed - in process]